tbuckley/cabot-search huggingface dataset:
PATH-09. Liquid biopsy of cerebrospinal fluid enables detecting and monitoring of<i>MYC/MYCN</i> amplification in pediatric CNS malignancies
Authors: Natalia Stepien, Christine Haberler, Julia Furtner-Srajer, Christian Dorfer, Thomas Czech, Daniela Lötsch-Gojo, Lisa Mayr, Alicia Baumgartner, Amedeo A Azizi, Andreas Peyrl, Irene Slavc, Leonhard Müllauer, Sibylle Madlener, Johannes Gojo
Journal: Neuro-Oncology (2022)

Abstract In the era of precision oncology, rapid molecular profiling as well as continuous monitoring of response to treatment or relapse are of increasing importance. We investigated digital droplet (dd)PCR for cerebrospinal fluid (CSF) derived cell-free (cf)DNA detection as a new method for rapid diagnosing of MYC/MYCN amplification in CNS malignancies - a patient collective with a dismal prognosis. Wet lab validated ddPCR probes for MYC were first investigated in D425 cells, a human medulloblastoma cell line with confirmed MYC amplification. Results of the methylation array of patients with stored CSF/serum samples (-80°C) were screened for patients with MYC/MYCN amplification. Five patients with medulloblastoma (group 3/4) and MYC-amplification and one patient with a diffuse glioma and MYCN-amplification were included in this study. ddPCR was performed on cfDNA isolated from CSF or serum. MYC amplification was detected by ddPCR in 28/33 (85%) CSF samples, with 4/5 negative samples being from one patient, and only one sample showing an unsuccessful analysis. MYC amplification was detectable in all longitudinal samples in 4/5 patients. 1/1 sample from the patient with MYCN amplific ation was positive in ddPCR. We were not able to detect MYC amplification in serum samples. Importantly, a turn-around time of only six hours from sample thawing/acquisition to result generation was easily achievable. Concluding, detection of MYC/MYCN-amplification in CSF by ddPCR is feasible in the clinical setting and allows for a rapid molecular diagnosis. MYC-amplification was constantly detectable in 4/5 patients with longitudinal CSF samples, which is in-line with the tumor burden our patients suffered from. Interestingly, the detectability in the patient’s serum was low, presumably due to the lower percentage of cell-free tumor (ct)DNA in serum when compared to CSF. Our results render ddPCR as a promising tool for bed-side molecular diagnosis and disease monitoring.
Outcomes of pulmonary embolism in patients with pancreatic cancer: A nationwide inpatient sample study.
Authors: Khaldun Obeidat, Ekrem Turk, Vaishali Deenadayalan, Catherine Weir, Jay Vakil, Pierre Alexander Rodriguez Alarcon, Kunnal Batra
Journal: Journal of Clinical Oncology (2022)

e16235 Background: Pancreatic cancer is considered one of the most aggressive cancers with five-year relative survival of 10.8% as per the national institute of health (NIH); Thromboembolism is a well-known complication of pancreatic cancer which contributes to increased morbidity, mortality and burden on the health care system. We attempted to evaluate the outcomes of pulmonary embolism in patients with pancreatic cancer. Methods: Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) was queried to identify Pulmonary embolism admissions between 2016-2018 In Adult patients with diagnosis of pancreatic cancer using International Classification of Disease 10 th Revision (ICD-10) codes. We evaluated mortality, Need for ventilation, Tissue plasminogen activator (TPA) administration, Embolectomy, Inferior vena cava (IVC) filter insertion and Acute kidney injury. Secondary outcomes included mean length of stay (LOS) and the mean cost of hospitalization. Results: A total 5335 admissions with PE and Pancreatic cancer were identified; in the baseline characteristics mean age was 67.4 at time of diagnosis with 51% being females and the white race constituted 73% of the total admissions. 385 patients (7%) died during hospitalization,165 patients (3%) required ventilation, 140 patients (2.6%) had TPA administration,560 patient (10.4%) had IVC inserted, 640 patients (12%) developed Acute kidney injury, and none had embolectomy. Mean length of stay was around 5 days and the mean cost of hospitalization was $12405. Conclusions: Pulmonary embolism increases mortality among patients with Pancreatic cancer; in addition to its effect on morbidity and burden on health care system; Efforts should be made to identify those with pancreatic cancer and considered high risk for Venous thromboembolism who may benefit from primary prophylaxis.
Cribriform cancer is equally visible to non-cribriform cancer on multiparametric MRI: An analysis using texture features
Authors: H. Izumi, S. Uehara, Y. Matsuoka, K. Yamamoto, Y. Nakamura, Y. Uchida, S. Fukuda, H. Tanaka, S. Yoshida, M. Yokoyama, K. Ohashi, Y. Fujii
Journal: European Urology (2022)
Molecular diagnostics to reduce inequity in breast cancer diagnosis.
Authors: Clement Adebayo Adebamowo, Emmanuel Ezeome, King-David Terna Yawe, Omobolaji Ayandipo, Olawale Badejo, Sally Nneoma Adebamowo, Izu Ben Achusi, Abike Fowotade, Gabriel Olabiyi Ogun
Journal: Journal of Clinical Oncology (2022)

548 Background: Modern management of breast cancer requires proper subtyping of the breast tumor to guide appropriate treatment and prognostication. However, there are barriers to availability of this resource in low- and middle-income countries (LMIC) which contributes to global inequalities in breast cancer management and outcomes. The non-availability is due to high cost, and lack of personnel and infrastructure required for immunohistochemistry (IHC), the current gold standard for subtyping. IHC results are affected by pre-analytic and analytic handling and are subjective. Alternative methods that are more objective, cost less and require less infrastructure and skilled personnel will improve access and reduce disparities. Methods: In the AFBRECANE Project, we compared the results of ER and PR subtyping of 1,000 breast cancer tumors from patients recruited from 5 clinical sites in Nigeria using IHC and Cepheid GeneXpert RNA STRAT4 biomarker assay at ACCME Lab in Nigeria and University of Maryland. Results: For ER, the sensitivities, specificities, and agreement between IHC and STRAT4 ranged from 50.0%, 71.4% and 59.4% to 77.1%, 80.0% and 78.5% while for PR, they ranged from 58.1%, 66.7% and 62.5% to 84.6%, 84.2% and 84.4%. Conclusions: The wide range of sensitivities, specificities, and agreement between IHC and STRAT4 in this study confirms the challenges of molecular subtyping of breast cancer in LMICs like Nigeria. Sustainable objective methods are sorely needed to improve diagnosis, treatment and prognostication, and reduce global disparities.
An Electromagnetically Controllable Microrobotic Interventional System for Targeted, Real‐Time Cardiovascular Intervention (Adv. Healthcare Mater. 11/2022)
Authors: Junsun Hwang, Sungwoong Jeon, Beomjoo Kim, Jin‐young Kim, Chaewon Jin, Ara Yeon, Byung‐Ju Yi, Chang‐Hwan Yoon, Hun‐Jun Park, Salvador Pané, Bradley J. Nelson, Hongsoo Choi
Journal: Advanced Healthcare Materials (2022)

Medical Robotics In article number 2102529 by Hongsoo Choi and co-workers, a proposed electromagnetically controllable microrobotic system can help interventional medical practitioners optimally manipulate interventional devices such as guidewires for the treatment of cardiovascular diseases. The system can be teleoperated, protecting medical staff from ionizing radiation.
Prevalence and perceptions of cannabis use among racially diverse patients with cancer pain: Results from a multi-site survey.
Authors: Brooke Worster, Rebecca Ashare, Salimah H. Meghani, Danielle Smith, Amy Allen Case, Preethi Selvan, Ayako Shimada, Greg D. Garber, Amy Leader
Journal: Journal of Clinical Oncology (2022)

12125 Background: While access to cannabis is prevalent among cancer patients 1 , unknowns persist about real-time use, perceived effectiveness in cancer pain management and impact on other medication use, including opioids. Moreover, racial disparities in cancer pain management persist 2-3 with Black patients more likely to have undiagnosed pain. 4 Studies on the intersection of cannabis, opioids, race and cancer pain are needed. As part of an NCI-funded initiative, we assessed the perceived effectiveness of cannabis vs. opioids for pain control by race. Methods: A survey was created by three Mid-Atlantic, cancer centers to examine self-reported cannabis use and knowledge, barriers and perceptions about cannabis among cancer patients. All sites assessed common core questions and included additional questions assessing cannabis and opioid use. Patients were eligible to participate if they were treated for cancer within the prior year. Surveys were distributed both by mail and electronically via REDCap. Results are compared separately by site. Results: In all, 2,734 patients are included in this analysis. Rates of cannabis use since diagnosis ranged from 32-41% of respondents, with similar rates of use between gender and race. Patients under age 65 more frequently reported cannabis use. Across sites, only 7-8% of patients reported currently using opioids. A sizable number patients who use cannabis reported using cannabis instead of opioids to treat pain. Of those using cannabis, most felt that cannabis was better in managing their pain than opioids, with Black patients reporting this much more frequently than White patients across two sites (Site A 62.2% vs 43.2%, Site B 77.78 vs 48.96%, Site C 50.0% vs. 65.5%). The most common reasons patients reported using cannabis instead of opioids included the perception that: “cannabis is safer” (80-82%), “cannabis is less addictive” (70-73%), and “cannabis has fewer side effects” (68-74%). Conclusions: Cannabis is frequently used by cancer patients, with many reporting use instead of opioids for pain management. Of those using cannabis for pain management, a significant majority felt that it is more effective than opioids. Black patients report cannabis as more effective than opioids for pain control more frequently than other races. Given the ongoing under-treatment of cancer pain in Black patients, more data is needed to understand whether cannabis is an effective tool to reduce disparities in cancer pain management. [Table: see text]
Parental inflammatory bowel disease and autism in children
Authors: Aws Sadik, Christina Dardani, Panagiota Pagoni, Alexandra Havdahl, Evie Stergiakouli, Jakob Grove, Golam M. Khandaker, Sarah A. Sullivan, Stan Zammit, Hannah J. Jones, George Davey Smith, Christina Dalman, Håkan Karlsson, Renee M. Gardner, Dheeraj Rai
Journal: Nature Medicine (2022)

Abstract Evidence linking parental inflammatory bowel disease (IBD) with autism in children is inconclusive. We conducted four complementary studies to investigate associations between parental IBD and autism in children, and elucidated their underlying etiology. Conducting a nationwide population-based cohort study using Swedish registers, we found evidence of associations between parental diagnoses of IBD and autism in children. Polygenic risk score analyses of the Avon Longitudinal Study of Parents and Children suggested associations between maternal genetic liability to IBD and autistic traits in children. Two-sample Mendelian randomization analyses provided evidence of a potential causal effect of genetic liability to IBD, especially ulcerative colitis, on autism. Linkage disequilibrium score regression did not indicate a genetic correlation between IBD and autism. Triangulating evidence from these four complementary approaches, we found evidence of a potential causal link between parental, particularly maternal, IBD and autism in children. Perinatal immune dysregulation, micronutrient malabsorption and anemia may be implicated.
The role of percutaneous renal tumor biopsy in frail patients with indeterminate small renal masses
Authors: G. Baiamonte, G. Rosiello, G. Fallara, A. Martini, D. Cignoli, G. Basile, G. Colandrea, G. Baiamonte, W. Cazzaniga, L. Nocera, A. Nini, I. Rowe, D. Canibus, G. Musso, F. Cei, C. Giancristofaro, M. Romani, A. Briganti, F. Montorsi, A. Salonia, A. Larcher, U. Capitanio
Journal: European Urology (2022)
Automatic identification of oncology patients with unsupervised phenotyping and AutoML.
Authors: Jingqing Zhang, Atri Vivek Sharma, Luis Bolanos Trujillo, Vibhor Gupta, Yike Guo
Journal: Journal of Clinical Oncology (2022)

e13547 Background: Recent studies suggest ICD codes often cannot characterise patients with specific diseases like oncology accurately in real-world clinical practice due to a high probability of miscoding, while manual inspection of millions of patients is not feasible as it is highly costly and slow. Therefore, we present an AI driven workflow, which leverages structured discrete values and unstructured textual data from Electronic Health Records (EHRs), to automatically identify cancer patients especially those who might be miscoded or undiagnosed. Methods: The proposed AI driven workflow is trained on 29637 and tested on 29339 patients from MIMIC-III database. First, the workflow builds patient profiles by leveraging the state-of-the-art unsupervised Natural Language Processing (NLP) method to extract phenotypic features from textual discharge summaries. Second, the workflow classifies if a patient has the risk of ovarian cancer (ICD-9: 183.0) or lung cancer (ICD-9: all subcodes of 162) based on their profiles using an Automated Machine Learning (AutoML) framework. Third, we improve the workflow through 100 gold-labelled patients out of the train set who are labelled as positive and negative ovarian (lung) cancer cases by three clinicians with consensus and we subsequently measure its performance against another 100 gold-labelled patients out of the test set and the entire test set with 29339 patients. Results: For ovarian cancer, on the 100 gold-labelled patients (52 ovarian cancer cases) out of the test set, the workflow achieves 0.877 AUCROC with precision 84.7% and sensitivity 96.2% whereas ICD codes have precision 94.6% and sensitivity 74.1%. On the entire test set with 29339 patients, the workflow identifies 111 ovarian cancer patients while ICD codes find only 38 patients which lead to 192% lifting. Similarly, for lung cancer, on the 100 gold-labelled patients (66 lung cancer cases) out of the test set, the workflow achieves 0.814 AUCROC with precision 88.7% and sensitivity 83.3% while ICD codes have precision 96.0% and sensitivity 72.7%. On the entire test set with 29399 patients, the workflow identifies 926 lung cancer patients while ICD codes find 585 patients which lead to 58% lifting. Conclusions: This study shows the AI driven workflow on textual clinical notes can help find more cancer patients with high accuracy especially those who are miscoded and undiagnosed by ICD codes. Since ICD codes are primarily used for billing purposes, this workflow also shows the opportunity to reconcile patient characteristics with ICD codes through the application of such novel AI at scale. Moreover, the results of this study have shown this approach can be scaled across other disease areas within oncology and beyond to help find new intelligence to characterise hard to diagnose conditions and improve patient outcomes through a significant improvement in speed and accuracy of screening and early diagnosis of patients.
Prognostic significance of therapy-induced myelosuppression in newly diagnosed glioblastoma.
Authors: Michael Weller, Felix Boakye Oppong, Maureen Vanlancker, Roger Stupp, Louis B. Nabors, Olivier L. Chinot, Wolfgang Wick, Matthias Preusser, Thierry Gorlia, Emilie Le Rhun
Journal: Journal of Clinical Oncology (2022)

2055 Background: Myelosuppression is the major toxicity encountered during temozolomide chemoradiotherapy for newly diagnosed glioblastoma. Methods: We assessed the association of myelosuppression (neutropenia, thrombocytopenia, anemia, lymphopenia) during temozolomide chemoradiotherapy alone or in combination with experimental agents with progression-free survival (PFS) or overall survival (OS) in 2073 patients with newly diagnosed glioblastoma enrolled into five clinical trials: CENTRIC, CORE, EORTC 26082, AVAglio, and EORTC 26981. A landmark analysis approached was used. For each primary association analysis, a significance level of 1.7% was used. Results: Lower neutrophil counts at baseline were associated with better PFS (p = 0.011) and OS (p &lt; 0.001), independently of steroid intake. Females experienced uniformly more myelotoxicity than males. Lymphopenia during concomitant chemoradiotherapy was associated with OS (p = 0.009): low-grade (1-2) lymphopenia might be associated with superior OS (HR 0.78, 98.3% CI 0.58-1.06) whereas high-grade (3-4) lymphopenia might be associated with inferior OS (HR 1.08, 98.3% CI 0.75-1.54). There were no associations of altered hematological parameters during concomitant chemoradiotherapy with PFS. During maintenance chemoradiotherapy, no significant association was found between any parameter of myelosuppression and PFS or OS, although exploratory analysis at 5% significance level indicated that either mild-to-moderate (HR 0.76, 95% CI 0.62-0.93) or high-grade lymphopenia (HR 0.65, 95% CI 0.46-0.92) were associated with superior OS (p = 0.013), but not PFS. Conclusions: The association of higher neutrophil counts at baseline with inferior PFS and OS requires further prospective evaluation. The link of therapy-induced lymphopenia to better outcome may guide the design for immunotherapy trials in newly diagnosed glioblastoma.
Cannabis-Based Products for Chronic Pain
Authors: Marian S. McDonagh, Benjamin J. Morasco, Jesse Wagner, Azrah Y. Ahmed, Rongwei Fu, Devan Kansagara, Roger Chou
Journal: Annals of Internal Medicine (2022)

Contemporary data are needed about the utility of cannabinoids in chronic pain.To evaluate the benefits and harms of cannabinoids for chronic pain.Ovid MEDLINE, PsycINFO, EMBASE, the Cochrane Library, and Scopus to January 2022.English-language, randomized, placebo-controlled trials and cohort studies (≥1 month duration) of cannabinoids for chronic pain.Data abstraction, risk of bias, and strength of evidence assessments were dually reviewed. Cannabinoids were categorized by THC-to-CBD ratio (high, comparable, or low) and source (synthetic, extract or purified, or whole plant).Eighteen randomized, placebo-controlled trials (n = 1740) and 7 cohort studies (n = 13 095) assessed cannabinoids. Studies were primarily short term (1 to 6 months); 56% enrolled patients with neuropathic pain, with 3% to 89% female patients. Synthetic products with high THC-to-CBD ratios (>98% THC) may be associated with moderate improvement in pain severity and response (≥30% improvement) and an increased risk for sedation and are probably associated with a large increased risk for dizziness. Extracted products with high THC-to-CBD ratios (range, 3:1 to 47:1) may be associated with large increased risk for study withdrawal due to adverse events and dizziness. Sublingual spray with comparable THC-to-CBD ratio (1.1:1) probably is associated with small improvement in pain severity and overall function and may be associated with large increased risk for dizziness and sedation and moderate increased risk for nausea. Evidence for other products and outcomes, including longer-term harms, were not reported or were insufficient.Variation in interventions; lack of study details, including unclear availability in the United States; and inadequate evidence for some products.Oral, synthetic cannabis products with high THC-to-CBD ratios and sublingual, extracted cannabis products with comparable THC-to-CBD ratios may be associated with short-term improvements in chronic pain and increased risk for dizziness and sedation. Studies are needed on long-term outcomes and further evaluation of product formulation effects.Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services. (PROSPERO: CRD42021229579).
First-line treatment in advanced renal cell carcinoma: A quasi-individual patient data meta-analysis
Authors: L. Nocera, A. Martini, G. Fallara, G. Basile, A. Larcher, G. Rosiello, D. Raggi, G. Malena, L. Marandino, F. Belladelli, P.I. Karakiewicz, A. Briganti, A. Salonia, F. Montorsi, U. Capitanio, A. Necchi
Journal: European Urology (2022)
Deubiquitinase OTUD3 regulates metabolism homeostasis in response to nutritional stresses
Authors: Na Zhou, Hailong Qi, Junjun Liu, Guangze Zhang, Jianping Liu, Ning Liu, Minglu Zhu, Xuyang Zhao, Chang Song, Zhe Zhou, Jingjing Gong, Ridong Li, Xinyu Bai, Yan Jin, Yongfeng Song, Yuxin Yin
Journal: Cell Metabolism (2022)
Kidney transplantation in patients ≥80 years: Retrospective multicenter study
Authors: J. Bertholle Gil, M.A. Narvaez Barros, J. Comas Farnés, F.J. Moreso Mateos, M.J. Perez Saez, J. Tort I Bardolet, J. Morote Robles, D. Serón Micas, D. Lorente Garcia, E. Miret Alomar, E. Trilla Herrara
Journal: European Urology (2022)
Detailed immunogenomic analysis of high dose IL-2 pharmacodynamic effects: A benchmark for next-generation IL-2-based immunotherapies.
Authors: Kirk Beebe, Joel Robert Eisner, Yoichiro Shibata, James M Davison, John Guo, Carol J. Farhangfar, Farhang Farhangfar, Joshua M. Uronis, Jill Mooney, Michael Vance Milburn, David Foureau, Richard L. White, Asim Amin, Marcos E Milla
Journal: Journal of Clinical Oncology (2022)

e16501 Background: High-dose interleukin-2 (HD IL-2) was the first approved immune-oncology (IO) agent based on proven clinical efficacy in renal cell carcinoma (RCC) and metastatic melanoma, but its use was limited due to significant toxicities. Multiple next-generation IL-2 agents designed to retain efficacy while improving tolerability are in development. Yet, understanding of genomic markers that define optimized target pharmacology is incomplete. Newer evaluation techniques not available at the time of previous HD IL-2 experience may allow for identification of pertinent genomic markers. In this retrospective study, we report for the first time, RNA sequencing (RNAseq) of peripheral blood mononuclear cell (PBMC) samples from metastatic (mRCC) patients before, during and after HD IL-2 treatment. Detailed immunogenomic responses to HD IL-2 treatment with insight into traditional flow cytometry (FC) are presented. Methods: PBMC samples were collected for n = 23 HD IL-2 treated mRCC patients between 2009 and 2015 on Day 1, 3 and 5. Patient samples underwent prior FC analysis described elsewhere (Foureau et al, 2014; Cancer Immunol. Immunother. 63(12)). RNAseq was performed using NovaSeq6000 (Illumina) paired end sequencing on bulk PBMC samples from immediately before (Day 1), during (Day 3) and post-treatment (Day 5) Cycle 1 and/or Cycle 2 of the first course of HD IL-2. Individual genes and signatures for immune and proliferation differences were analyzed. Results: RNAseq analysis of PBMC samples demonstrated that CD8+ T cells transiently decreased in the blood during treatment but recovered to baseline on Day 5, and CD4 Treg cells increased on Day 3 and Day 5, which confirmed prior FC findings. TCR clonality was unchanged which indicates that T cell recovery and expansion is widespread and not driven by a specific subset of T cells. Additional notable insights included increased monocytes at Day 3, with the opposite for NK and B cells (Day 3 decrease and Day 5 expansion). Using a novel GeneCentric proliferation signature, increased expression was noted on Day 3 and Day 5 vs. Day 1, reflecting pronounced IL-2 induced proliferation. Conclusions: Immunogenomics provided further detail regarding IL-2 activity in addition to recapitulating several parameters from FC. Expression analysis of minimally invasive PBMC samples demonstrates the importance of this novel genomic approach to understand the pharmacology of IL-2 and related derivatives.